rs2297328

Positions:

• chr10-24524398-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_019590.5(KIAA1217):​c.2532A>G​(p.Thr844=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 1,614,102 control chromosomes in the GnomAD database, including 5,210 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1698 hom., cov: 33)
  • Exomes 𝑓: 0.056 (3512 hom.)
• Consequence: KIAA1217 NM_019590.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.34

Genes affected

KIAA1217 (HGNC:25428): (KIAA1217) Predicted to be involved in embryonic skeletal system development. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-4.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1217	NM_019590.5	c.2532A>G	p.Thr844=	synonymous_variant	13/21	ENST00000376454.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1217	ENST00000376454.8	c.2532A>G	p.Thr844=	synonymous_variant	13/21	1	NM_019590.5	A2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17462 AN: 152142 Hom.: 1679 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.0594

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0914

GnomAD3 exomes AF: 0.0810 AC: 20346 AN: 251338 Hom.: 1345 AF XY: 0.0758 AC XY: 10291 AN XY: 135848

Gnomad AFR exome AF: 0.277

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.0337

Gnomad EAS exome AF: 0.158

Gnomad SAS exome AF: 0.0872

Gnomad FIN exome AF: 0.0558

Gnomad NFE exome AF: 0.0426

Gnomad OTH exome AF: 0.0593

GnomAD4 exome AF: 0.0558 AC: 81539 AN: 1461842 Hom.: 3512 Cov.: 31 AF XY: 0.0554 AC XY: 40263 AN XY: 727222

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.0972

Gnomad4 ASJ exome AF: 0.0342

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.0867

Gnomad4 FIN exome AF: 0.0551

Gnomad4 NFE exome AF: 0.0424

Gnomad4 OTH exome AF: 0.0652

GnomAD4 genome AF: 0.115 AC: 17512 AN: 152260 Hom.: 1698 Cov.: 33 AF XY: 0.116 AC XY: 8628 AN XY: 74474

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.0912

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.0913

Gnomad4 FIN AF: 0.0594

Gnomad4 NFE AF: 0.0414

Gnomad4 OTH AF: 0.0919

Alfa AF: 0.0605 Hom.: 776

Bravo AF: 0.125

Asia WGS AF: 0.128 AC: 446 AN: 3478

EpiCase AF: 0.0405

EpiControl AF: 0.0387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0030
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2297328; hg19: chr10-24813327; COSMIC: COSV56813717;